PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling
| Autor: | Yingyu Chen, Beiqi Hongdu, Xin Lin, Liujing Qu, Ge Li, Chentong Xu, Dan Xia |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Class I Phosphatidylinositol 3-Kinases Biophysics Biology medicine.disease_cause Biochemistry 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Line Tumor medicine Autophagy Humans Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Protein kinase C Protein Kinase C Gene knockdown Osteosarcoma Oncogene TOR Serine-Threonine Kinases Cell Biology Cell biology Isoenzymes 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Signal transduction Carcinogenesis Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 470(2) |
| ISSN: | 1090-2104 |
| Popis: | The atypical protein kinase C isoform PRKC iota (PRKCI) plays a key role in cell proliferation, differentiation, and carcinogenesis, and it has been shown to be a human oncogene. Here, we show that PRKCI overexpression in U2OS cells impaired functional autophagy in normal or cell stress conditions, as characterized by decreased levels of light chain 3B-II protein (LC3B-II) and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, PRKCI knockdown by small interference RNA resulted in opposite effects. Additionally, we identified two novel PRKCI mutants, PRKCI(L485M) and PRKCI(P560R), which induced autophagy and exhibited dominant negative effects. Further studies indicated that PRKCI knockdown-mediated autophagy was associated with the inactivation of phosphatidylinositol 3-kinase alpha/AKT-mammalian target of rapamycin (PIK3CA/AKT-MTOR) signaling. These data underscore the importance of PRKCI in the regulation of autophagy. Moreover, the finding may be useful in treating PRKCI-overexpressing carcinomas that are characterized by increased levels of autophagy. |
| Databáze: | OpenAIRE |
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